Vitamin B12 malabsorption occurs in patients with pancreatic disease and in rats subjected to partial pancreatic extirpaton. The observed vitamin B12 malabsorption is corrected by the administration of hog pancreatic extract. Subfractionation of hog pancreatic extract has isolated a heat labile, soluble, acid-stable constitutent, free of gastric intrinsic factor activity, between 10,000 and 30,000 molecular waight with proteolytic properties which corrects the vitamin B12 malabsorption in both humans and rats. The administration of trypsin or chymotrypsin also restores vitamin B12 absorption to normal, but the mechanism of action of these proteolytic enzymes on vitamin B12 absorption has not been defined. Hog gastric intrinsic factor or autologous gastric juice, previously collected from patients with pancreatic insufficiency and vitamin B12 malabsorption, can be treated with proteolytic enzymes, the proteolytic enzymes removed, and the gastric intrinsic factor (hog or human) readministered to the patients. These enzyme treated sources of gastric intrinsic factor now fully correct vitamin B12 malabsorption. The chromatographic, electrophoretic, antigenic, and absorption promoting properties of gastric intrinsic factor will be investigated before and after treatment with proteolytic enzymes. The interaction of this treated gastric intrinsic factor with each of the steps of vitamin B12 absorption will be investigated. The intestinal secretions from patients and rats with pancreatic insufficiency will be studied to determine whether their endogenous pancreatic proteolytic enzymes are quantitatively or qualitatively different from control subjects with normal vitamin B12 absorption. Bibliographic references: In vitro Activation of Gastric Intrinsic Factor by Pancreatic Proteolytic Enzymes. P. Toskes, Gastroenterology, 66: 868, 1974; Evidence that the Pancreatic Factor Enhancing B12 Absorption is Neither Trypsin nor Chymotrypsin. P. Toskes, G. Francis, G. Smith and E. Sander, Clinical Research, 23: 258, 1975.